Obesity is a serious human health problem that often increases the incidence of other diseases, such as heart disease, stroke, diabetes, and even cancer. Understanding the cellular and molecular underpinnings of obesity will therefore undoubtedly lead to a substantial human health benefits. Recently, a hormone (leptin, or ob) was described in mammals that acts as a "lipostat"; sensing the body's adiposity and regulating appetite and metabolism to maintain constant fat stores. Leptin has the potential to explain many aspects of lipid function (including human obesity), and because of this it has been the focus of intense research effort over the past five years. Almost exclusively, the research effort to understand leptin function has used mammalian models, presumably due to the obvious applicability to humans. We assert that a comparative approach (e.g. studying leptin function in evolutionarily distant model- organisms) has utility in understanding leptin function. The comparative approach has been successfully applied to other physiological questions, solving problems not easily approached with mammalian models (i.e. myoglobin function). We have the first data that point to leptin's existence in.fishes, and we submit that experiments with fish leptin may uncover unique aspects of leptin function in all vertebrates. The proposed experiments are designed to understand the physiological effects of leptin, and determine its primary structure in a bony fish (Lepomis cyanellus, the green sunfish). Results of the proposed research will l) determine the effect of leptin on metabolic fuel partitioning in fish and 2) identify potential function domains in leptin via comparative sequence analysis.